ABSTRACT
Background: Many countries are promoting booster SARS-CoV-2 vaccination campaigns as the COVID-19 pandemic continues. Incremental short-term adverse events after two SARS-CoV-2 vaccinations have been reported in healthy individuals.1,2 However, data on incremental short-term adverse events in patients with various immune-mediated infammatory diseases (IMIDs) after repeated SARS-CoV-2 vaccination is scarce. Objectives: We report risk factors for short-term adverse events in IMID patients after SARS-CoV-2 vaccination. Methods: Self-reported daily questionnaires on adverse events in the frst seven days after SARS-CoV-2 vaccination were obtained from individuals participating in an ongoing prospective multi-arm multicenter cohort study on SARS-CoV-2 vaccination in patients with various IMIDs in the Netherlands (T2B! immunity after SARS-CoV-2). Clinically relevant adverse events were defned as systemic adverse advents lasting longer than two days or hindering daily activities. Adjusted relative risks for developing clinically relevant adverse events were calculated using a logistic mixed-effects model. Results: Data of 2081 patients and 178 healthy controls were obtained. Infammatory bowel disease (N:480), Multiple sclerosis (N:343) and Rheumatoid arthritis (N:266) were the largest disease groups. Adjusted relative risks for relevant adverse events are presented in Figure 1. Third vaccination was not associated with increased risk on adverse events when compared to a second vaccination (aRR: 0.93 95% CI: 0.84-1.02). Patients with IMIDs were at increased risk for developing adverse events after vaccination when compared to controls (aRR: 1.16 95% CI: 1.01-1.34). Female sex (aRR 1.43 95% CI: 1.32-1.56), age below 50 (aRR 1.14 95% CI: 1.06-1.23) and a preceding SARS-CoV-2 infection (aRR: 1.14 95% CI: 1.01-1.29) were also associated with increased risk of adverse events following vaccination. Allergic reactions and hospital admission were uncommon (0.67% and 0.19% respectively);7.4% and 6.8% of patients reported adverse events impacting daily life on day seven after second and third vaccination, respectively. Data on increase in disease activity of the IMID following vaccination are currently being investigated. Conclusion: A third SARS-CoV-2 vaccination was not associated with an increased risk on short-term clinically relevant adverse events when compared to a second vaccination. Although patients with IMIDs may be slightly more at risk to develop adverse events after SARS-CoV-2 vaccination, most adverse events were transient and disappeared within seven days. This message should reassure IMID patients who are hesitant on booster vaccination. Data on potential IMID fare-ups after vaccination will follow.
ABSTRACT
Background The aim of this study was to investigate the effect of various immunosuppressants on the humoral immune responses after vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). Methods The Target to B! SARS-CoV-2 study is a multicentre study, taking place in 7 Dutch academic hospitals. Patients with the following IMIDs were recruited: Crohn’s disease (CD), ulcerative colitis (UC), auto-immune hepatitis, rheumatic (e.g. rheumatoid arthritis), neurological (e.g. multiple sclerosis) and dermatological IMIDs (e.g. atopic dermatitis). Patients were recruited based on immunosuppressants (table 1) and previous SARS-CoV-2 infection. The control group consisted of healthy subjects and IMID patients without immunosuppressants. SARS-CoV-2 receptor binding domain (RBD) antibodies were measured 28 days after completed SARS-CoV-2 vaccination. Seroconversion was defined as anti-RBD IgG >4 AU/mL. In this , we focus on therapies relevant for inflammatory bowel diseases (IBD) and present results for these treatments from patients with IBD, but also other IMIDs. Results Numbers of recruited patients with each immunosuppressant are shown in table 1. Amongst these patients, 312 patients had CD and 176 UC, the rest was diagnosed with another IMID. Seroconversion was reduced in patients receiving sphingosine 1-phosphate (S1P) modulators (all multiple sclerosis patients) while seroconversion was similar to controls in the other treatment groups. However, use of Anti-tumour necrosis factor (TNF), methotrexate, janus kinase (JAK) inhibitor monotherapy and all combination therapies (except for corticosteroids combined with other immunosuppressants) were associated with reduced Sars-CoV-2 antibody titres. Patients with a previous SARS-CoV-2 infection had higher median antibody titres after second vaccination than those without a previous SARS-CoV-2 infection. The type of IMID did not affect seroconversion rates. Conclusion No immunosuppressant, registered for IBD, reduced the rates of seroconversion after vaccination against SARS-CoV-2. Some immunosuppressants were associated with lower antibody titres. However, the clinical relevance of lower antibody titres remains unknown. S1P modulators, had a clear negative impact on the humoral response against SARS-CoV-2 after vaccination. This might be relevant in the future as this therapy is currently being approved for UC. Disease aetiology did not impair immunity against SARS-CoV-2 immunity after vaccination. Disclaimer: Absolute numbers of antibody titres and rates of seroconversion will be reported at the conference and are not reported in this as this might negatively impact the current submission process.
ABSTRACT
OBJECTIVE: The objective of this study was to measure humoral responses after SARS-CoV-2 vaccination in MS patients treated with ocrelizumab (OCR) compared to MS patients without disease modifying therapies (DMTs) in relation to timing of vaccination and B-cell count. METHODS: OCR treated patients were divided into an early and a late group (cut-off time 12 weeks between infusion and first vaccination). Patients were vaccinated with mRNA-1273 (Moderna). B-cells were measured at baseline (time of first vaccination) and SARS-CoV-2 antibodies were measured at baseline, day 28, 42, 52 and 70. RESULTS: 87 patients were included (62 OCR patients, 29 patients without DMTs). At day 70, seroconversion occurred in 39.3% of OCR patients compared to 100% of MS patients without DMTs. In OCR patients, seroconversion varied between 26% (early group) to 50% (late group) and between 27% (low B-cells) to 56% (at least 1 detectable B-cell/µL). CONCLUSIONS: Low B-cell counts prior to vaccination and shorter time between OCR infusion and vaccination may negatively influence humoral response but does not preclude seroconversion. We advise OCR treated patients to get their first vaccination as soon as possible. In case of an additional booster vaccination, timing of vaccination based on B-cell count and time after last infusion may be considered.